Project Summary: The long-term objectives of this application are twofold: first, to explore the role of the sympathetic nervous system in the pathophysiology of metabolic control;and second, for the applicant to acquire the skill set needed to become an independent investigator. The metabolic syndrome is associated with an increased risk of cardiovascular disease and premature death and the control of key metabolic processes such as lipolysis, glucose regulation, and energy expenditure are linked to the sympathetic nervous system. We believe sympathetic activation is the "missing link" to the metabolic syndrome. In this proposal, we describe a collaborative, multidisciplinary approach designed to study the relationship of muscle sympathetic activity (MSNA) in humans to insulin sensitivity, lipolysis, and energy expenditure. This plan takes advantage of the expertise of the applicant"s mentors and consultants to take a unique approach to this problem. This research plan will also serve as a tool for the development of the applicant, who is at a perfect stage in his career for the K23 program. A strong, experienced, well funded mentorship team is in place that will ensure that the applicant will develop into an independent clinical researcher positioned to obtain long-term independent funding. A comprehensive career development plan has been developed by the applicant and his mentors that takes advantage of the commitment of the applicant's department and institution to developing young clinician scientists and the research environment at Mayo Clinic, including its CTSA. Relevance: This project has immediate and important public health relevance. The metabolic syndrome is a major contributor to morbidity and mortality world-wide and little is known about its basic causes. By understanding the link between the autonomic nervous system and metabolic dysfuntion, we may be able to better prevent and treat this important disease.